Experiments were completed examining the interaction of complement with Trypanosoma cruzi, Leishmania major, and Toxoplasma gondii. Final purification and characterization of the C3 convertase inhibitor produced by trypomastigotes of T. cruzi was completed. The molecule is an 87-93kd glycoprotein, P.I. 5.6-5.8 expressed in infective trypomastigote but not non-infectious epimastigote forms. Functionally, the trypomastigote molecule is identical to human decay accelerating factor: it prevents formation and accelerates decay of the classical and alternative pathway C3 convertases. There is a correlation between the lytic activity of Chagasic serum and the capacity of antibodies in the serum to recognize the C3 convertase inhibitor by immunoprecipitation and to block the functional activity of the inhibitor. The mechanism of resistance to serum killing for metacyclic promastigotes of Leishmania major was further clarified. Both serum sensitive long phase promastigotes and serum-resistant metacyclic promastigotes activates complement efficiently, and a C5b-9 complex is formed on the parasite membrane. With metacyclic promastigotes, the C5b-9 complex is shed and is not lytic because it fails to insert into hydrophobic domains of the Leishmania membrane. Tachyzoites of Toxoplasma gondii are resistant to serum killing because limited C3 and C5b-9 are deposited during incubation in serum. Bound C3b is rapidly cleaved to the lytically inactive iC3b form. Complement deposition is increased and the site of deposition is altered by lytic monoclonal antibodies for tachyzoites.